The overall goal of this Program Project is to understand at the atomic level how three families of DNA repair enzymes recognize and process their substrates. The central goal of the Bioinformatics Core is to make use of sequence, structure, and function data for the design and interpretation of experiments that will achieve the goal of the Program Project. The Aims of the Research Projects involve testing hypotheses about natural enzymes and site-directed mutants of these enzymes using functional measurements and X-ray crystallography. The Bioinformatics Core will provide tools that use existing knowledge of the structure and function of these families to identify natural enzymes and site-directed mutants for these studies. The results of the experimental work will be used by the Bioinformatics Core for designing subsequent experiments. The Aims of the Bioinformatics Core are: Aim 1: To provide infrastructure for information management and analysis. The Core will provide stable and secure information management as well as flexible querying mechanisms and a broad spectrum of bioinformatics tools. The information will include primary data, experimental designs, and inferred results. The analysis tools will include existing applications and custom analysis tools that enhance research productivity. Aim 2: To develop phylogenetic tree-based methods for selecting natural enzymes for functional and structural studies. Aim 3: To develop phylogenetic tree-based methods for selecting site-directed mutants of natural enzymes for functional and structural studies.